The health of the oral cavity is maintained by salivary secretions. Our past studies focused on understanding mechanisms of saliva formation, their alteration during pathology, and developing novel methods to treat salivary dysfunction. During this reporting period we continued to utilize gene transfer technology to alter salivary epithelial cells to address clinical and biological questions. We have extended studies using adeno-associated viral vectors (serotype 2), demonstrating stable expression in, and transgene product secretion from, murine submandibular glands (SMGs) for >2 months. We also continued our studies on the hybrid adeno-retroviral vector that we reported last year, focusing on understanding the mechanism of genomic integration achieved. We previously showed that transgenes contain sorting signals recognized by salivary glands in vivo, leading to specific patterns of polarized protein secretion. Our focus this year was on the manipulation these secretory patterns to enhance endocrine-like secretion. We continued our studies on aquaporin water channels associated with salivary secretion and showed that AQP8 is localized to the basolateral membranes of rat SMGs. We also continued to make progress towards the development of an orally implantable, first generation artificial salivary gland. Our clinical studies continue to focus on determining if the salivary dysfunction accompanying Sjogren's syndrome can be ameliorated by immunomodulatory therapy.